rs141076138

Variant names:

• chr3-46923616-G-A
• rs141076138
• NM_001277074.2:c.297C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-46923616-G-A
• chr3-46923616-G-C
• chr3-46923616-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001277074.2(CCDC12):​c.297C>T​(p.Ile99Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,599,472 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00062 (2 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (1 hom.)
• Consequence: CCDC12 NM_001277074.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

Genes affected

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.479 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC12	NM_001277074.2	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 4 of 7	ENST00000683445.1	NP_001264003.1
CCDC12	NM_144716.6	c.336C>T	p.Ile112Ile	synonymous_variant	Exon 5 of 8		NP_653317.2
CCDC12	NR_102269.2	n.350C>T		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC12	ENST00000683445.1	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 4 of 7		NM_001277074.2	ENSP00000508011.1

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152192 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000116 AC: 27 AN: 232462 Hom.: 0 AF XY: 0.0000558 AC XY: 7 AN XY: 125382

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.0000815 AC: 118 AN: 1447162 Hom.: 1 Cov.: 30 AF XY: 0.0000626 AC XY: 45 AN XY: 718820

Gnomad4 AFR exome AF: 0.00229

Gnomad4 AMR exome AF: 0.000231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.000268

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152310 Hom.: 2 Cov.: 33 AF XY: 0.000524 AC XY: 39 AN XY: 74476

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000395 Hom.: 1

Bravo AF: 0.000771

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.68
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141076138; hg19: chr3-46965106;